Introduction

The body has an intricate system for transporting oxygen from the surrounding atmosphere to each and every cell in order to sustain normal cell, organ and whole-body function. However, the amount of oxygen available for the oxygen-requiring cellular processes is determined by numerous factors, including oxygen delivery (which, in turn, is determined by blood flow, haematocrit, haemoglobin oxygen saturation, oxygen extraction from the blood, diffusion distance, diffusion gradient, diffusion coefficient etc.) and local oxygen consumption (which is determined by mitochondrial efficiency and energy-consuming cellular processes, such as active transport, protein translation, contraction, radical production, enzymatic activity etc.). Increasing interest has been directed towards understanding these complex interactions and what role defective tissue oxygenation plays in disease development. The kidney is unique in the sense that it is a very wellperfused organ, receiving approximately 25% of cardiac output, but only contributing to approximately 8–10% of total body oxygen consumption. Furthermore, the kidney is unique in the sense that it does not exhibit a robust hyperaemic response when oxygen demand increases. Rather, the opposite occurs, with oxygen consumption often increasing with increased renal blood flow. The vascular arrangement, consisting of countercurrent systems, allows for oxygen to be shunted from arteries to veins. As a result, oxygen delivery to the kidney tissue may be limited, rendering the kidney highly susceptible to acute and chronic changes in oxygen balance. However, it was not until recently that Fine et al. presented the hypothesis that tissue hypoxia is a common pathway to chronic kidney disease (CKD). In 2006, Clinical and Experimental Pharmacology and Physiology presented a Frontiers in Research Series on Kidney Oxygenation, comprising six review papers. This initiative was continued in October 2011, when Uppsala University had the great pleasure to host some of the current world experts in Uppsala for a meeting solely devoted to kidney oxygenation. This was indeed a tremendous experience and, as a result of this meeting, five up-to-date review papers, covering most of what was discussed during these days of fabulous science, are presented in this Frontiers in Research series ‘Kidney Oxygenation in Health and Disease’. As you will find, there is some degree of overlap between the different papers, which reflects the integrative nature of this field of research. The paper by Nangaku et al. summarizes the current knowledge about regulation of hypoxia inducible factor (HIF) in kidney disease. The authors conclude that there is a complex interaction between acute kidney injury (AKI) and CKD via intrarenal tissue hypoxia and HIF activation. A further understanding of these mechanisms may reveal novel therapeutic targets to counter the progression of kidney disease. The paper by Evans et al. details recent advances in our understanding of the regulation of kidney oxygenation by haemodynamic factors. Recently, growing interest has been devoted to mathematical models of oxygen transport in both the cortex and medulla. Because of the vast amount of data available in the literature, and in combination with reasonable approximations, these attempts prove fruitful and relevant when identifying novel ideas in need of further attention. The paper by Hansell et al. proposes a new hypothesis incorporating increased renal oxygen consumption with subsequent intrarenal tissue hypoxia as a central mechanism for the development of CKD. Detailed attention is also devoted to describing the current knowledge of the intricate relationship between tubular electrolyte transport and oxygen use and how these changes contribute to diabetic and hypertensive kidney disease. The paper by Singh et al. summarizes the current knowledge as to how deranged intrarenal oxygen metabolism contributes to AKI and CKD. In that paper, knowledge from both basic science and clinical studies is included and it is proposed that interventions to prevent the development of intrarenal hypoxia may be a novel approach to reduce the onset and progression of these conditions. Finally, the paper by Liss et al. delineates the methodology available to non-invasively study kidney oxygenation, which should allow the roles of deranged oxygen metabolism in the development of AKI and CKD to be established definitively. There are still many scientific questions and methodological hurdles that need to be addressed before we can fully appreciate the role of kidney oxygenation in health and disease. However, opportunities to focus on and discuss these issues certainly inspire new thinking and ideas as to how to move the field forward. Clinical and Experimental Pharmacology and Physiology (2013) 40, 104–105